SCHEME 1
AlCl3‚6H2O/KI/H2O/CH3CN: A New
Alter n a te System for Deh yd r a tion of
Oxim es a n d Am id es in Hyd r a ted Med ia
Monalisa Boruah and Dilip Konwar*
Organic Chemistry Division, Regional Research Laboratory,
J orhat 785 006, Assam, India
dkonwar@yahoo.co.uk
Received J anuary 2, 2002
Abstr a ct: Dehydration of oximes and amides to nitriles was
carried out using the AlCl3‚6H2O/KI/H2O/CH3CN system. It
produced isoquinoline derivatives 8a -c (Bischler Naperi-
alski reaction) when reacted with amides 7a -c in hydrated
media. Also, the keto oximes produced anilides (Beckmann
rearrangement) with the system under the same reaction
conditions.
Dehydration of oximes and amides to nitriles is an
important transformation in organic syntheses. In the
last 40 years, a number of efficient methods have been
developed for the dehydration of oximes and amides to
nitriles,1a,b and the search for better reagents is still
continues.1c Also, it is reported that these conversions
may be performed either by using bacterial enzymes with
aldoximes1d or by employing oximes ethers under basic
conditions.1e But the methods developed so far have their
own limitations, for example, the use of extremely
anhydrous reaction conditions,1 very corrosive and mois-
ture sensitive reagents,1-3 use of toxic and hazardous
chemicals,4,5 cumbersome workup procedures and prob-
lems associated with waste disposal,6,7 and lack of
versatility in the transformations conducted in hydrated
media.1d,e
we now wish to report the AlCl3‚6H2O/KI/CH3CN system
as a new, efficient, and versatile alternate system for the
dehydration of oximes and amides to nitriles and in-
tramolecular cyclodehydration of amides to isoquinolines
derivatives and keto oximes to anilides in hydrated
media.
Aldoxime (Scheme 1, compound 1a ) was reacted with
the AlCl3‚6H2O/KI/CH3CN system [1 equiv of AlCl3‚6H2O/
KI, 1 equiv of 1a ] in a mixture of acetonitrile and water
(5:1) at reflux temperature for 6 h, and after workup with
5% ammonium hydroxide solution, it produced p-meth-
oxybenzonitrile (Scheme 1, compound 2a ) in 95% yield
without formation of triazine11 in the reaction mixture.
It was observed that the acid-susceptible1a groups like
methyl ether (Scheme 1, compound 1a) and furan (Scheme
1, compound 2h ) were unaffected under the reaction
conditions and both E and Z isomers of the oximes could
be converted to nitriles (in most cases the oximes used
were the mixture of E and Z isomers). Similarly, the
amides (Scheme 1, compounds 5a ,b) under the same
reaction condition could be converted to its corresponding
nitriles (Scheme 1, compounds 6a ,b) in good yields in the
hydrated media. Also, when the system was treated with
the amides (Scheme 1, compounds 7a -c), intramolecular
cyclodehydration (Bischler Naperialski reaction) oc-
curred13 and resulted industrially important isoquinoline
derivatives (Scheme 1, compounds 8a -c), the key inter-
mediates for dextromethorphan [anti-tussive drug] and
its analogues.14 Also, It was observed that when the
The chemistry and potentialities of AlCl3‚6H2O as a
reagent in organic synthesis has been less explored,8
particularly in the presence of KI in hydrated media.9 In
continuation of our research in aluminum chemistry,1a,8-10
(1) (a) Konwar, D.; Boruah, R. C.; Sandhu, J . S Tetrahedon Lett.
1990, 34, 1063-64 and references therein. (b) Comprehensive Organic
Transformation, A guide to functional group preparation; Larock, L.
C., Ed.; VCH, Inc.: New York, 1989; pp 991-993 and references
therein. (c) Bose, S.; J ayalakshmi, B.; Goud, P. R. Synthesis 1999, 10,
1724-1726. (d) Kato, Y.; Ooi, R.; Asano, Y. J . Mol. Cat. B: Enzym.
1999, 6, 249-256. (e) Hegarty, A. F.; Tuohey, P. J . J . Chem. Soc.,
Perkin Trans. 2 1980, 1313-17.
(2) (a) Olah, G. A.; Narang, S. C.; Salem, G. F. Sythesis 1980, 659.
(b) Denis, J . N.; Krief, A. J . Chem. Soc., Chem. Commun. 1980, 544.
(3) Olah, G. A.; Vankar, Y. D.; Garcia-Luna, A. Synthesis 1979, 227.
(b) Carotti, A.; Campagna, F.; Ballini, R. Synthesis 1979, 56.
(4) Sosnovsky, G.; Krogh, J . A. Synthesis 1978, 703.
(5) (a) Ho, T. L.; Wong, C. M. Synth. Commun. 1975, 5, 423. (b)
Shimada, J .; Ushigome, A.; Itabashi, K. YukiGosei Kagaku Kyokaishi
1977, 35, 913; Chem. Abstr. 1978, 88, 120753.
(6) (a) Dulcere, J . P. Tetrahedron Lett. 1981, 22, 1599. (b) Cooper,
D.; Trippett, S. Tetrahedron Lett. 1979, 19, 1725.
(10) (a) Dutta, D. K.; Konwar, D. Tetrahedron Lett. 2000, 41, 6227-
29. (b) Konwar, D.; Boruah, R. C.; Sandhu, J . S. Synthesis 1990, 337-
40. (c) Konwar, D.; Boruah, R. C.; Sandhu, J . S. Chem. Ind. 1989, 191-
192. (d) Konwar, D.; Boruah, M.; Sarmah, G.; Bhattachareyya, N. K.;
Borthakur, N.; Goswami, B. N.; Boruah, K. R. J . Chem. Res.in press.
(11) J ohnson, F.; Madronero, R. In Advances in Heterocyclic Chem-
istry; Katritzky, A. R., Ed.; Academic Press: New York, 1966; Vol. 6,
pp 95-146.
(7) Vowinkel, E.; Bartel, J . Chem. Ber. 1974, 107, 1221.
(8) (a) Dutta, D. K.; Konwar, D. J . Chem. Res. 1998, 266-267. (b)
Dutta, D. K.; Konwar, D.; Sandhu, J . S. Ind. J . Chem. 1995, 34B, 725.
(c) Yamamatsu, S.; Yamaguchi, T.; Yakota, K. U.S. Patent, 60,40,472,
March 21, 2000, filed Oct 23, 1997. (d) Akieda, H.; Sato, N.; Mita, R.;
Umemoto, M. U.S. Patent 5,221,769, J une 22 1993, filed Dec 27, 1990.
(9) Boruah, M.; Konwar, D. Syn. Lett. 2001, 6, 795-796.
(12) Organic Reactions; J ohn-Wiley & Sons: London, 1960; Vol. II,
pp 1-158.
(13) Organic Reactions; J ohn-Wiley & Sons: London, 1951; Vol. VI,
pp 74-150.
10.1021/jo020005+ CCC: $22.00 © 2002 American Chemical Society
Published on Web 09/07/2002
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J . Org. Chem. 2002, 67, 7138-7139